Patients with Congenital Disorders of Glycosylation (CDGs) and other monogenic syndromes presenting with severe allergic disease in association with connective tissue abnormalities are actively being recruited and studied. A number of clinical assays have been developed in the laboratory in order to accomplish these goals: lectin-based flow cytometry is employed to characterize N-glycan abnormalities; ddPCR assays have been developed to perform tryptase genotyping and assay isoform-specific gene expression. Using molecular genetic techniques, we continue to characterize defects we have identified in discrete immune pathways and in glycosylation processes. To do so, we employ a number of techniques including cellular transfection and pathway inhibition with small molecules, siRNAs, shRNAs, and antibodies. As we characterize the role that altered glycosylation plays in allergic diseases and reactions, we seek to devise ways to manipulate these pathways to limit or alter disease pathogenesis.